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. 2024 Jun 3;7(6):e2418486.
doi: 10.1001/jamanetworkopen.2024.18486.

Clinical Outcomes for BRCA Pathogenic Variant Carriers With Breast Cancer Undergoing Breast Conservation

Kerollos Nashat Wanis  1 , Henry M Kuerer  1 , Susie X Sun  1 , Kelly K Hunt  1 , Alexa C Glencer  1 , Mediget Teshome  1 , Anthony Lucci  1 , Roi Weiser  1 , Helen Johnson  1 , Benjamin D Smith  2 , Angelica M Gutierrez  3 , Simona F Shaitelman  2 , Banu K Arun  3
Affiliations

Clinical Outcomes for BRCA Pathogenic Variant Carriers With Breast Cancer Undergoing Breast Conservation

Kerollos Nashat Wanis et al. JAMA Netw Open. .

Abstract

Importance: Although most women with BRCA-associated breast cancer choose bilateral mastectomy, current guidelines support breast-conserving therapy as an option. As the indications for genetic testing expand and targeted therapies emerge, understanding the outcomes of breast-conserving therapy in the population of patients choosing breast conservation is important.

Objective: To describe the clinical outcomes of women with BRCA-associated breast cancer who were treated with breast-conserving therapy, including the risks of ipsilateral and contralateral cancer events and bilateral mastectomy-free survival.

Design, setting, and participants: This cohort study conducted at a single-institution academic national comprehensive cancer center included 172 women identified from a prospectively maintained database who had pathogenic BRCA1/2 variants and were treated with breast-conserving therapy from January 1, 1977, to December 31, 2021.

Main outcomes and measures: Clinical and pathologic characteristics for patients with BRCA1 and BRCA2 were compared, and estimates of overall survival, bilateral mastectomy-free survival, distant disease-free survival, risk of ipsilateral breast cancer, and risk of contralateral cancer were computed.

Results: The cohort included 172 women (mean [SD] age, 47.1 [11.7] years), with 42 (24.4%) receiving a diagnosis of breast cancer prior to 40 years of age. Compared with BRCA2 variant carriers (80 [46.5%]), women with BRCA1 variants (92 [53.5%]) were younger at breast cancer diagnosis and tended to have more advanced tumors, which were more likely to be hormone receptor negative and higher grade. At a median follow-up of 11.8 years (IQR, 5.7-18.2 years), estimates of 10-year survival and risk were: overall survival, 88.5% (95% CI, 83.1%-94.2%); bilateral mastectomy-free survival, 70.7% (95% CI, 63.3%-78.9%); risk of an ipsilateral breast cancer event, 12.2% (95% CI, 5.8%-18.2%); and risk of contralateral cancer, 21.3% (95% CI, 13.3%-28.6%). Risks continued to increase after 10 years of follow-up.

Conclusions and relevance: In this cohort study, although women with breast cancer and pathogenic BRCA1/2 variants treated with breast-conserving therapy had above-average risks of ipsilateral and contralateral breast cancer events, most did not have another cancer event and remained bilateral mastectomy free. These findings may be useful for informing patients with BRCA variants choosing breast conservation.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Kuerer reported receiving personal fees from NEJM Group Inc, UpToDate Inc, and McGraw-Hill Professional Inc outside the submitted work. Dr Hunt reported receiving personal fees from ArmadaHealth Medical and AstraZeneca; grants to the institution from Cairn Surgical Research, Eli Lilly & Co, and Lumicell outside the submitted work. Dr Teshome reported receiving conference travel and accommodations from Endomag Ltd. Dr Smith reported receiving salary support from Varian Medical Systems; grants from Artidis; and and royalty and equity interest in Oncora Medical outside the submitted work. Dr Shaitelman reported receiving contracted research support from Artidis and Exact Sciences; receiving grants from the National Institutes of Health; and serving as a consultant for Lumicell and Becton, Dickinson & Co outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Overall Survival and Distant Disease-Free Survival Stratified by BRCA Variant Status
Displayed P value is from log-rank test.
Figure 2.
Figure 2.. Risk of Ipsilateral Breast Tumor Event and Risk of Contralateral Breast Cancer Stratified by BRCA Variant Status
Displayed P value is from log-rank test.
Figure 3.
Figure 3.. Bilateral Mastectomy-Free Survival and Bilateral Mastectomy-Free Survival Due to an Ipsilateral or Contralateral Breast Cancer Event Stratified by BRCA Variant Status
Displayed P value is from log-rank test.
See this image and copyright information in PMC

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